The objective of this project is to probe molecular mechanisms of olfactory transduction. To date we have examined the active site of the Schiff base-forming enzyme acetoacetate decarboxylase and have developed techniques for irreversible labelling. We have also developed a behavioral assay for inhibition of receptors in the olfactory epithelium of tiger salamanders and have observed a chemically-induced selective anosmia. We now seek to use labelling techniques that have proved suitable for acetoacetate decarboxylase to radiolabel possible olfactory ketone receptors. Our specific aims are (1) To refine the behavioral assay for chemical inhibition of olfactory receptors in laboratory animals. (2) To examine the binding of odorant molecules to olfactory receptors; (3) To develop a procedure for irreversibly fixing the odorant-receptor bond, and to assess its efficacy in vivo using our behavioral assay; (4) To isolate proteins that are labelled when this fixing procedure is applied to the olfactory epithelium of tiger salamanders; (5) To characterize labelled proteins that are likely candidates for olfactory receptors by preparing antibodies to Schiff base-forming proteins and testing their effects on the olfactory epithelium using our behavioral assay.